High L-Valine Concentrations Associate with Increased Oxidative Stress and Newly-Diagnosed Type 2 Diabetes Mellitus: A Cross-Sectional Study

Abstract

Wen Hu,1,2,* Panpan Yang,3,* Zhenzhen Fu,1 Yongqing Wang,4 Ying Zhou,1 Zhengqin Ye,1 Yingyun Gong,1 Aijie Huang,1 Luning Sun,4 Yang Zhao,5 Tao Yang,1 Zhong Li,6,7 Xian-Cheng Jiang,8 Weinan Yu,2 Hongwen Zhou1,6 1Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Huai’an Hospital of Xuzhou Medical College, Huai’an, Jiangsu, People’s Republic of China; 3Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical College, Huai’an, Jiangsu, People’s Republic of China; 4Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5School of Public Health Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 6Key Laboratory of Rare Metabolic Diseases, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 7Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 8Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY, USA*These authors contributed equally to this workCorrespondence: Hongwen Zhou, Department of endocrinology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel [phone]-6893, Fax [phone], Email [email protected] Weinan Yu, Department of Endocrinology and Metabolism, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, 223001, People’s Republic of China, Email [email protected]: Branched-chain amino acids (BCAAs) are essential AAs which are widely used as antioxidants in patients with liver and kidney dysfunction. However, BCAAs are strongly correlated with insulin resistance (IR) and diabetes. This study aimed to evaluate the relationship among BCAAs, oxidative stress, and type 2 diabetes mellitus (T2DM) in a Chinese population.Methods: Anthropometric and biochemical examinations were performed in 816 individuals who participated in the Huai’an Diabetes Prevention Program. Serum BCAAs concentrations were measured by hydrophilic interaction chromatography-tandem mass spectrometric method. Oxidative stress was evaluated by malondialdehyde (MDA) as an index of lipid peroxidation and the superoxide dismutase (SOD) activity.Results: A total of 816 participants were divided into three groups: normal glucose metabolism (NGM), prediabetes, and newly-diagnosed diabetes mellitus (NDM). Subjects in NDM group show higher MDA and lower SOD levels than subjects in other groups. L-Val levels positively correlated with MDA levels and negatively with SOD in NDM groups. After adjusting for T2DM risk factors, high L-Val levels were significantly associated with higher BMI, WC, FPG, increased LnTG and decreased HDL-C. L-Val was also independently associated with NDM (OR 1.06, 95% CI 1.02– 1.10; P = 0.005). Furthermore, the odds ratios for NDM among participants with high L-Val (≥ 35.25μg/mL) levels showed a 2.25-fold (95% CI 1.11– 4.57; P = 0.024) increase compared to participants with low L-Val (< 27.26 μg/mL) levels after adjusting for MDA and confounding factors.Conclusion: High serum L-Val levels are independently associated with oxidative stress, thus promoting IR and NDM. Further study should be done to clarify the mechanism.Keywords: branched chain amino acids, oxidative stress, new diagnosed type 2 diabetes mellitus, hydrophilic interaction chromatography-tandem mass spectrometric method

Keywords

• branched chain amino acids
• oxidative stress
• new diagnosed type 2 diabetes mellitus
• hydrophilic interaction chromatography-tandem mass spectrometric method